Oxidative Phosphorylation

Electron transport chain

Series of intermediate carriers that transfer electrons from NADH and FADH₂ to O₂.

Where does the ETC take place?

Inner mitochondrial membrane

Final electron acceptor in ETC?

O₂

Proton gradient in the ETC

Higher concentration of protons (lower pH) in the intermembrane space and lower concentration of protons (higher pH) in the mitochondrial matrix

The reduction potential ___________ from the first electron carrier to the last electron carrier

Increases

Where are the complexes located?

The inner mitochondrial membrane

Which complexes pump protons to from the mitochondrial matrix to the intermembrane space?

I, III, and IV

What drives ATP synthesis in the ETC

The proton gradient powers ATP synthase

ETC Complex I

NADH-CoQ oxidoreductase

Transfers electrons from NADH to CoQ (Ubiquinone)

Contains iron-sulfur clusters used to oxidize NADH

ETC Complex II

Succinate-CoQ oxidoreductase

Transfers electrons from FADH₂ to CoQ (Ubiquinone)

Contains iron-sulfur clusters used to oxidize FADH₂

Also used in TCA cycle step 6 to make fumarate from succinate

Electron carrier from complex I and II to complex III

CoQ/Ubiquinone (oxidized)

CoQH₂/Ubiquinol (reduced)

ETC Complex III

CoQH₂-Cyt-c oxidoreductase

Transfers electrons from CoQH₂ to reduced cytochrome c

______ is hydrophilic and travels ______ the inner membrane

Cytochrome C; above

______ is hydrophobic and travels ______ the inner membrane

Coenzyme Q; within

What is the role of cytochromes in the electron transport chain (ETC)?

Transfer electrons through redox reactions in their heme groups

Take electrons from CoQ (Complex III) and bring them to O₂ (Complex IV)

What is the role of the heme group in cytochromes during electron transport?

Use its iron to transfer electrons by switching between Fe²⁺ and Fe³⁺

Q Cycle

The specific reactions that transfer electrons from CoQH₂ to Cyt-c

Occurs in complex III

ETC Complex IV

Cytochrome c oxidase

Transfers electrons from Cyt-c to O₂

Has intermediate electron acceptors

• Cyt a

• Cu²⁺

• Cyt a₃

Electron transport in Complex IV

Cyt-c → Cyt-a → Cu²⁺ → Cyt-a₃ → O₂

Coupling Factor

“Couples” Oxidation (electron transfer in ETC) and Phosphorylation (ATP synthesis)

Refers to ATP synthase

How does ATP synthase work as a rotating molecular motor?

Two parts:

• F₀ (in the membrane) lets H⁺ flow through, spinning like a motor

• F₁ (in the matrix) uses that spin to change shape and make ATP from ADP + Pi
  This rotation-powered process makes 3 ATP per full turn

How many protons are pumped through the inner mitochondrial membrane due to 1 molecule of NADH?

4 H⁺ from complex I

+ 4 H⁺ from complex III

+ 4 H⁺ from complex IV

= 12 H⁺ Total

How many protons are pumped through the inner mitochondrial membrane due to 1 molecule of FADH₂?

4 H⁺ from complex III

+ 4 H⁺ from complex IV

= 8 H⁺ Total

How many protons does it take to make 1 ATP?

4 protons

How many ATP is produced per molecule of NADH?

12 H⁺ pumped to the intermembrane space / 4 protons per turn of ATP synthase = 3 ATP

How many ATP is produced per molecule of FADH₂?

8 H⁺ pumped to the intermembrane space / 4 protons per turn of ATP synthase = 2 ATP

Blockers of Oxidative Phosphorylation

Stop electron flow by inhibiting specific complexes.

Examples of ETC Blockers

Cyanide - blocks complex IV → O₂ does not get reduced into H₂O → stops ATP production

Amytal - blocks complex I → no e^- from NADH → ATP production slows, but doesn’t stop because Complex II still provides electrons

Uncouplers of oxidative phosphorylation

Disconnect electron transport and atp synthesis → ETC keeps running but less ATP is made

Electrons released as heat because they don’t get used by ATP synthase

ETC needs to work harder to form a proton gradient to power ATP synthase

2,4 - Dinitrophenol

Uncoupler of Oxidative phosphorylation, results in dangerous weight loss

Brown adipose/fat

Uncouples oxidative phosphorylation to generate heat in baby mammals

What harmful oxygen by-products can form during oxidative phosphorylation?

• Superoxide ion (•O₂⁻)

• Hydroxyl radical (•OH)

• Hydrogen peroxide (H₂O₂)

Superoxide ion (•O₂⁻)

can damage proteins and DNA

Hydroxyl radical (•OH)

initiate chain reactions in membranes

Hydrogen peroxide (H₂O₂)

can convert into hydroxyl radicals